CD47-a novel prognostic predicator in epithelial ovarian cancer and correlations with clinicopathological and gene mutation features.

BACKGROUND: Epithelial ovarian cancer (EOC) is insensitive to immunotherapy due to its poor immunogenicity; thus, suitable biomarkers need to be identified for better prognostic stratification and individualized treatment. CD47 is a novel immunotherapy target; however, its impact on EOC prognosis is controversial and correlation with genetic features is unclear. The aim of this study was to investigate the prognostic significance of CD47 and its correlations with biological behaviors and genetic features of EOC. METHODS: Immunohistochemistry (IHC) and next-generation sequencing (NGS) were performed to examine expressions of CD47, PD-L1, and genomic mutations in the tissue samples of 75 EOC patients. Various clinicopathologic and genomic features were then evaluated to determine their correlation with CD47 expression. Kaplan-Meier analysis and Cox regression analysis were used to identify independent prognostic factors. Risk score modeling was then established, and the predictive capacity of this model was further confirmed by nomogram analysis. RESULTS: CD47 was mainly expressed in the tumor cell membrane and cytoplasm, and the rate of high CD47 expression was 63.7%. CD47 expression was associated with various clinicopathological factors, including FIGO stage, CA125 and HE4 value, presence of multidisciplinary surgeries, presence and volume of ascites, lymph-node metastasis, Ki-67 index and platinum-resistant, as well as genetic characteristics like BRCA mutation, HRD status, and TP53 mutation in EOC. Patients with high CD47 expression showed worse prognosis than the low-expression group. Cox regression analysis demonstrated that CA125, CD47, and BRCA mutation were independent factors for EOC prognosis. Patients were then categorized into high-risk and low-risk subgroups based on the risk score of the aforementioned independent factors, and the prognosis of the high-risk group was worse than those of the low-risk group. The nomogram showed adequate discrimination with a concordance index of 0.777 (95% CI, 0.732-0.822). The calibration curve showed good consistency. CONCLUSION: CD47 correlated with various malignant biology and genetic characteristics of EOC and may play pivotal and multifaceted roles in the tumor microenvironment of EOC Finally, we constructed a reliable prediction model centered on CD47 and integrated CA125 and BRCA to better guide high-risk population management.

Novel predictors for identifying cervical minimal deviation adenocarcinoma patients with poor prognosis: a long-term observational study in a tertiary centre.

PURPOSE: To elucidate the clinicopathological features and prognostic factors of minimal deviation adenocarcinoma (MDA) of the uterine cervix, a clinically rare but highly invasive disease. METHODS: This was a retrospective, observational, real-world study of 43 patients with pathologically confirmed MDA at the Obstetrics and Gynaecology Hospital of Fudan University between November 2010 and November 2021. Baseline clinicopathological data were collected and reviewed. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were investigated by univariate and multivariate Cox proportional hazards analyses. RESULTS: Chief complaints included irregular vaginal discharge and/or bleeding (74.4%). Preoperative diagnosis was difficult, the detection rate was low (36.8%), all cases showed endophytic lesions, and 88.4% had deep stromal invasion, with biologically aggressive characteristics. The ovarian metastasis rate was high (16.3%, 7/43). The median maximum diameter of the tumour (MDOT) was 4.3 cm (range, 0.5-8.0 cm). MDOT was significantly associated with OS (P = 0.009), and the optimal cut-off value to define bulky MDA was 5.5 cm (P < 0.0001, χ= 21.161) using X-tile software. Independent prognostic factors included MDOT (HR = 10.095, P = 0.001) and ovarian metastasis (HR = 5.888, P = 0.008) for OS and MDOT (HR = 3.944, P = 0.028), ovarian metastasis (HR = 9.285, P = 0.001), and deep infiltration (HR = 3.627, P = 0.048) for PFS. CONCLUSION: Endophytic lesion development and ovarian metastasis are likely in MDA. A bulky tumour and ovarian metastasis indicate a worse prognosis. Given the special biological features of MDA, it is more appropriate to use 5.5 cm as the threshold for defining a bulky tumour than it is to use 4 cm. Ovary removal should be given higher priority to improve prognosis.

Cytoreductive surgery is feasible in patients with limited regional platinum-resistant recurrent ovarian cancer.

INTRODUCTION: To evaluate the efficacy of cytoreductive surgery versus chemotherapy for the treatment of limited regional, platinum-resistant ovarian cancer (PROC). MATERIALS AND METHODS: The clinical records of all patients with PROC treated in our center between March 2015 and March 2022 were retrospectively reviewed. We compared the oncology outcomes of patients who received cytoreduction or chemotherapy alone at relapse and presented information about postoperative adjuvant chemotherapy. RESULTS: Among 52 patients with limited regional recurrence, 40.4% (21/52) underwent cytoreduction because of platinum resistance, and 59.6% (31/52) received chemotherapy alone. No residual disease (R0) was achieved in 20 patients (95.2%). The severe morbidity rate within 30 days after the surgery was 15%. The median follow-up was 70.6 months. Compared with the chemotherapy alone group, the surgery group with R0 had better progression-free survival (PFS) (10.6 vs. 5.1 months; hazard ratio (HR) = 0.421; P = 0.0035) and post-relapse survival (PRS) (32.6 vs. 16.3 months; HR = 0.478; P = 0.047), but there was no difference in overall survival (OS) between the two groups. Laparoscopy is associated with lesser intraoperative blood loss with no differences in survival and postoperative complications compared to the open approach (P = 0.0042). Subgroup survival analysis showed that compared with chemotherapy alone, surgery prolonged PFS in patients regardless of tumor size (greater than or equal to 4 cm or less). Surgery group patients who achieved R0 had an objective response rate (ORR) of 36.8% (7/19), among whom 40% (4/10) received platinum rechallenge chemotherapy and 33.3% (3/9) were administered non-platinum chemotherapy. CONCLUSION: When well-selected PROC patients with limited regional recurrence achieved R0, their outcomes were superior to those of patients who received only chemotherapy with an acceptable morbidity rate. Laparoscope technology could be a reliable alternative surgical approach. The reintroduction of platinum agents may be considered following surgery. Further analyses in a larger population are warranted to elucidate the risks and benefits of this surgery and adjuvant chemotherapy strategy.

The combined signatures of G protein-coupled receptor family and immune landscape provide a prognostic and therapeutic biomarker in endometrial carcinoma.

G protein-coupled receptors (GPRs) are one of the largest surface receptor superfamilies, and many of them play essential roles in biological processes, including immune responses. In this study, we aim to construct a GPR- and tumor immune environment (TME-i)-associated risk signature to predict the prognosis of patients with endometrial carcinoma (EC). The GPR score was generated by applying univariate Cox regression and the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression in succession. This involved identifying the differentially expressed genes (DEGs) in the Cancer Genome Atlas-Uterine Corpus Endometrioid Carcinoma (TCGA-UCEC) cohort. Simultaneously, the CIBERSORT algorithm was applied to identify the protective immune cells for TME score construction. Subsequently, we combined the GPR and TME scores to establish a GPR-TME classifier for conducting clinical prognosis assessments. Various functional annotation algorithms were used to conduct biological process analysis distinguished by GPR-TME subgroups. Furthermore, weighted correlation network analysis (WGCNA) was applied to depict the tumor somatic mutations landscapes. Finally, we compared the immune-related molecules between GPR-TME subgroups and resorted to the Tumor Immune Dysfunction and Exclusion (TIDE) for immunotherapy response prediction. The mRNA and protein expression of GPR-related gene P2RY14 were, respectively, validated by RT-PCR in clinical samples and HPA database. To conclude, our GPR-TME classifier may aid in predicting the EC patients' prognosis and immunotherapy responses.

Do ethnic chinese older adults with epithelial ovarian cancer survive a poorer prognosis?

BACKGROUND: The risk of suffering epithelial ovarian cancer (EOC) for women increases with age evidently, while the prognosis of older EOC patients remain unclear. Against the backdrop of the accelerate aging process in China, this paper investigates whether the older EOC patients have a lower overall survival probability than the younger patients based on the sample of ethnic Chinese population. METHODS: A total of 323 ethnic Chinese patients diagnosed as epithelial ovarian cancer were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We compared the overall survival probability between the younger group (< 70 years) and the older patients group (≥ 70 years). Survival curves were drawn using the Kaplan-Meier method, comparisons among different subgroups were evaluated using log-rank tests, and independent prognostic factors were identified by univariate and multivariate Cox regression analyses. RESULTS: 43 patients were (13.3%) in the older patients group and 280 (86.7%) in the younger group. The distribution patterns between two groups were significantly different with regard to marital status, histologic type and FIGO stage. The median overall survival (OS) was significantly longer in the younger group than the older patients group (not reached vs. median 39 months, p < 0.05). The multivariate analysis demonstrated that the age (The older vs. the younger, HR: 1.967, P = 0.007), primary tumor laterality (HR: 1.849, P = 0.009), and FIGO stage (III vs. I, HR: 3.588, P = 0.001; and IV vs. I, HR: 4.382, P = 0.001; respectively) remained as important risk factors while Histology (HGSOC vs. CCOC, HR: 0.479, P = 0.025; and LGSOC/MOC/EC vs. CCOC, HR: 0.390, P = 0.034; respectively) and the number of lymph node dissected more than 10 was a protective factor (HR: 0.397, P = 0.008). In an analysis of 104 pairs of patients matched on the basis of the propensity score, the older patients group had significantly lower overall mortality (HR = 2.561, P = 0.002). CONCLUSION: Ethnic Chinese Older EOC patients have a worse prognosis than the younger patients.

Blocking CD47-SIRPα Signal Axis as Promising Immunotherapy in Ovarian Cancer.

Among the three primary gynecological malignancies, ovarian cancer has the lowest incidence but the worst prognosis. Because of the poor prognosis of ovarian cancer patients treated with existing treatments, immunotherapy is emerging as a potentially ideal alternative to surgery, chemotherapy, and targeted therapy. Among immunotherapies, immune checkpoint inhibitors have been the most thoroughly studied, and many drugs have been successfully used in the clinic. CD47, a novel immune checkpoint, provides insights into ovarian cancer immunotherapy. This review highlights the mechanisms of tumor immune evasion via CD47-mediated inhibition of phagocytosis and provides a comprehensive insight into the progress of the relevant targeted agents in ovarian cancer.

A novel defined risk signature of endoplasmic reticulum stress-related genes for predicting the prognosis and immune infiltration status of ovarian cancer.

Endoplasmic reticulum (ER) stress, as an emerging hallmark feature of cancer, has a considerable impact on cell proliferation, metastasis, invasion, and chemotherapy resistance. Ovarian cancer (OvCa) is one of the leading causes of cancer-related mortality across the world due to the late stage of disease at diagnosis. Studies have explored the influence of ER stress on OvCa in recent years, while the predictive role of ER stress-related genes in OvCa prognosis remains unexplored. Here, we enrolled 552 cases of ER stress-related genes involved in OvCa from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts for the screening of prognosis-related genes. The least absolute shrinkage and selection operator (LASSO) regression was applied to establish an ER stress-related risk signature based on the TCGA cohort. A seven-gene signature revealed a favorable predictive efficacy for the TCGA, International Cancer Genome Consortium (ICGC), and another GEO cohort (P<0.001, P<0.001, and P=0.04, respectively). Moreover, functional annotation indicated that this signature was enriched in cellular response and senescence, cytokines interaction, as well as multiple immune-associated terms. The immune infiltration profiles further delineated an immunologic unresponsive status in the high-risk group. In conclusion, ER stress-related genes are vital factors predicting the prognosis of OvCa, and possess great application potential in the clinic.

A durable response to programmed cell death 1 blockade in a multidrug-resistant recurrent ovarian cancer patient with HLA-B44 supertype: A case report.

Relapsed/refractory ovarian cancer, especially platinum resistance recurrence, remains a major therapeutic challenge. Here, we present the case of a patient with recurrent ovarian clear cell carcinoma (OCCC) who failed to respond to multiline chemotherapy and target therapy but achieved an immune complete response (iCR) with programmed cell death 1 (PD-1) inhibitor treatment. The overall survival (OS) was 59 months, and the recurrence-free survival (RFS) was 34 months after immunotherapy, which was counting. Meantime, molecular testing results revealed that traditional biomarkers for immunotherapy, including PD-L1 expression, microsatellite instability (MSI), and tumor mutational burden (TMB), were negative. HLA-B44 (B*18:01) supertype was confirmed by sequence-based HLA typing. This case raises the possibility that ovarian cancer patients with multidrug resistance may still benefit from PD-1 inhibitor therapy, even if PD-L1 pathology is negative.

Novel prognostic nomograms to assess survival in high-grade serous ovarian carcinoma after surgery and chemotherapy: a retrospective cohort study from SEER database.

Background: Despite high-grade serous ovarian carcinoma (HGSOC) being the most common epithelial ovarian cancer, it is a heterogenous group of tumors with several histological subtypes. The goal of our study was to develop specifical models to predict the survival of actively treated, HGSOC. Methods: This retrospective cohort study included patients with HGSOC who had undergone surgery and chemotherapy between the years of 2010 and 2016 using the Surveillance, Epidemiology, and End Results (SEER) database. A total of 3,788 cases were randomly divided into a training (n=2,591) and test set (n=1,197). Cox-LASSO algorithm and cross validation (based on lambda.1se) were used to identify survival factors in the training set. Nomograms were created and internally validated. We used Harrell's C-statistic to assess discrimination. The performance of each nomogram was evaluated using calibration plots. The clinical benefit of our models was evaluated using a decision curve analysis. Results: The significant prognostic factors were marital status, age, lymph node (LN) dissection, tumor size, residual disease, and the International Federation of Obstetrics and Gynecology (FIGO) stage, which were utilized to develop the nomogram for accurately predicting 3- and 5-year overall survival (OS). Among the above factors, except for marital status, the others were included in the model for cancer-specific survival (CSS). The C-indices for OS and CSS achieved 0.679 [95% confidence interval (CI): 0.660 to 0.699] and 0.678 (95% CI: 0.658 to 0.698), respectively, in the training set and 0.662 (95% CI: 0.633 to 0.690) and 0.680 (95% CI: 0.653 to 0.707), respectively, in the test set. The good consistency was illustrated using calibration plots. In comparison with models including only FIGO or the AJCC staging system, C-index in our study were increased by 4.5-7.0% for the development test and by 6.7-7.9% for the validation test. In addition, the nomograms had a bigger range of threshold probabilities in the decision curve analysis (DCA) curves. The high-risk subgroup had significantly less favorable survival than the low-risk subgroup. Conclusions: The present study indicated that the low-cost nomograms could be used as a potential prognostic tool specially for predicting survival in patients with HGSOC. Given the relatively small C-index, we still need to build a more accurate model to predict survival of HGSOC.

Neuroendocrine neoplasms of the ovary: an analysis of clinicopathological characteristics and prognosis with a focus on histological grading.

OBJECTIVE: Ovarian neuroendocrine neoplasm is a rare and highly heterogeneous neoplasm. This study is aimed to describe its demographic and clinicopathological features and identify its prognostic factors. METHODS: Clinical data of 399 patients diagnosed with ovarian neuroendocrine neoplasms between 2004 and 2016 in the Surveillance, Epidemiology, and End Results (SEER) database were analysed retrospectively. Survival curves were drawn using the Kaplan-Meier method, comparisons among different subgroups were evaluated using log-rank tests, and multivariate Cox regression analyses identified independent prognostic factors. RESULTS: The five-year survival rates of patients with different histological types (carcinoid tumour, neuroendocrine carcinoma and special type of carcinoid tumour) were 25.5%, 96.1% and 75.0%, respectively (P < 0.001). Multivariate Cox analysis revealed that in carcinoid tumours, advanced FIGO stage was the only predictor. Additionally, no significant difference was observed among stages II, III and IV using the log-rank test. In neuroendocrine carcinoma, an advanced FIGO stage and high-grade differentiation were risk factors, while chemotherapy was a protective factor. Among all ovarian neuroendocrine neoplasms with a known histological differentiation status, no significant difference was observed among different histological types; only high-grade differentiation was an independent risk factor, and chemotherapy was a protective factor. CONCLUSIONS: Patients with neuroendocrine carcinomas and carcinoid tumours of an advanced FIGO stage have a poor prognosis. Poor differentiation of neuroendocrine carcinomas indicates a short survival time, and adjuvant chemotherapy appears to be effective. Histological differentiation of ovarian neuroendocrine neoplasms is the most potent prognostic factor comparing to other known factors. Taken together, ovarian neuroendocrine neoplasms might be better classified as low- or high-grade ones rather than the currently used classification based on histological types in the future.

Efficient charge separation and visible-light response in bilayer HfS2-based van der Waals heterostructures.

Two-dimensional (2D) hafnium disulfide (HfS2) has been synthesized and is expected to be a promising candidate for photovoltaic applications, and at the same time the hexagonal BN sheet (h-BN) and graphene-like C3N4 sheet (g-C3N4) have also been fabricated and are expected to be applied in photocatalysis. In this work, we employ hybrid density functional theory to investigate HfS2-based van der Waals (vdW) heterojunctions for highly efficient photovoltaic and photocatalytic applications. HfS2/h-BN and HfS2/g-C3N4 heterostructures with direct bandgaps and efficient charge separation are both typical type-II semiconductors and have potential as photovoltaic structures for solar power. Moreover, compared with h-BN and g-C3N4 single-layers, HfS2/h-BN heterostructures with 6% tensile strain and HfS2/g-C3N4 heterostructures with 9% tensile strain have moderate bandgaps, whose optical absorption is obviously enhanced in the ultraviolet-visible (UV-VIS) light range and whose bandedges are suitable for photocatalytic water splitting. HfS2/h-BN heterostructures with 6% applied strain, being different from HfS2/g-C3N4 heterostructures with 9% strain, possess a direct bandgap and show complete separation of the photoinduced electron-hole pairs. Thus the HfS2/h-BN heterojunction with 6% strain has bright prospects for use in visible light photocatalytic water splitting to produce hydrogen.

Band gap engineering of SnS2 nanosheets by anion-anion codoping for visible-light photocatalysis.

SnS2 nanosheets with three atom thickness have previously been synthesized and it has been shown that visible light absorption and hydrogen evolution through photocatalytic water splitting are restricted. In the present study, we have systematically investigated the electronic structures of anionic monodoped (N and P) and codoped (N-N, N-P, and P-P) SnS2 nanosheets for the design of efficient water redox photocatalysts by adopting first principles calculations with the hybrid HSE06 functional. The results show that the defect formation energies of both the anionic monodoped and all the codoped systems decrease monotonically with the decrease of the chemical potential of S. The P-P codoped SnS2 nanosheets are not only more favorable than other codoped systems under an S-poor condition, but they also reduce the band gap without introducing unoccupied impurity states above the Fermi level. Interestingly, although the P-P(ii) codoped system gives a band gap reduction, this system is only suitable for oxygen production and not for hydrogen evolution, which indicates that it may serve as a Z-scheme photocatalyst for water splitting. The P-P(i) codoped system may be a potential candidate for photocatalytic water splitting to generate hydrogen because of the appropriate band gap and band edge positions, which overcome the disadvantage that the pure SnS2 nanosheet is not beneficial for hydrogen production. More importantly, the result of optical absorption spectral analysis shows that the P-P(i) codoped SnS2 nanosheet absorbs a longer wavelength of the visible light spectrum as compared to the pristine SnS2 nanosheet. The P-P(I) codoped system with a lower doping concentration also has an absorption shift towards the visible light region.

A two-dimensional layered CdS/C2N heterostructure for visible-light-driven photocatalysis.

In this work, we employ hybrid density functional theory calculations to design a two-dimensional layered CdS/C2N heterostructure for visible light photocatalytic water splitting to produce hydrogen. The calculation results show that the conduction band minimum (CBM) and the valence band maximum (VBM) of C2N monolayers are lower than those of CdS nanosheets by about 0.76 eV and 0.44 eV, respectively. The type-II band alignment, density of states, Bader charge analysis, and charge density difference of the CdS/C2N heterostructure indicate that the photogenerated electrons migrate from the CdS monolayer to the C2N monolayer, favoring the separation and transfer of photogenerated charge carriers, which restrains the recombination of photogenerated carriers and enhances the photocatalytic efficiency. The calculated band gap and optical absorption spectra reveal that the two-dimensional layered CdS/C2N heterostructure may be a potential photocatalyst for photo-electrochemical water splitting because of its appropriate band gap and excellent visible light absorption behavior. Moreover, the electronic and optical properties of the CdS/C2N heterostructure can be effectively modulated by the strain. These findings suggest that the C2N sheets are a promising candidate as metal-free co-catalysts for CdS photocatalysts, and also provide valuable information for experimentalists to design highly active and efficient visible light photocatalysts for water splitting.